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Epilepsy and Anti epileptic drugs

Epilepsy and Anti epileptic drugs. Cellular mechanism of epilepsy. Classification of epileptic drugs. Pharmacological action of epilepsy. Treatment of epilepsy.

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Prepared by A. Gowtham Sashtha 1st M.Pharm
Department of pharmacology
K.M College of pharmacy, Madurai – 625107.
Epilepsy &
Anti-epileptic drugs
Epilepsy 
Anti-epileptic drugs
Definition of seizure  epilepsy
Seizure ?
✧ A seizure is a proximal event characterised by abnormal (or)
excessive hypersynchronous discharge of brain neurone activities.
Epilepsy ?
✧ Epilepsy can be define as the chronic conditions of seizure
disorder or group of disorder characterized by seizures that
usually recure unpredictably in the absence of a provoking factors.
Classification of seizure
1) Partial seizures
2) Generalized Seizures
3) Unclassified seizure
4) Status epilepticus
Types of seizure  epilepsy
I)Partial seizures (common 80% of patients)
1) Simple Partial Seizure
location : Cortical origin
Do not cause loss of consciousness.
Symptoms :
Motor-convulsive jerking, chewing motions, lip smacking.
Sensory-Paresthesias,
Autonamic-Sweating, flushing, pupil dilation.
Behaviour-Hallucination,dysphasia
2)Complex partial seizure
location : Temporal lobe area.
Symptoms :
Impairment of consciousness
Confused behaviour
Emotional changes
Olfactory hallucination.
3)Secondary generalized seizure
This seizure occurs evolves in to generalized tonic
clonic seizures with loss of consciousness.
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Epilepsy and Anti epileptic drugs

  • 1. Prepared by A. Gowtham Sashtha 1st M.Pharm Department of pharmacology K.M College of pharmacy, Madurai – 625107. Epilepsy & Anti-epileptic drugs Epilepsy Anti-epileptic drugs
  • 2. Definition of seizure epilepsy Seizure ? ✧ A seizure is a proximal event characterised by abnormal (or) excessive hypersynchronous discharge of brain neurone activities. Epilepsy ? ✧ Epilepsy can be define as the chronic conditions of seizure disorder or group of disorder characterized by seizures that usually recure unpredictably in the absence of a provoking factors.
  • 3. Classification of seizure 1) Partial seizures 2) Generalized Seizures 3) Unclassified seizure 4) Status epilepticus
  • 4. Types of seizure epilepsy
  • 5. I)Partial seizures (common 80% of patients) 1) Simple Partial Seizure location : Cortical origin Do not cause loss of consciousness. Symptoms : Motor-convulsive jerking, chewing motions, lip smacking. Sensory-Paresthesias, Autonamic-Sweating, flushing, pupil dilation. Behaviour-Hallucination,dysphasia
  • 6. 2)Complex partial seizure location : Temporal lobe area. Symptoms : Impairment of consciousness Confused behaviour Emotional changes Olfactory hallucination. 3)Secondary generalized seizure This seizure occurs evolves in to generalized tonic clonic seizures with loss of consciousness.
  • 7. II) Generalized seizure location : Affecting whole brain. 3types 1) Idiopathic epilepsies ➜Age related ➜Genetic related 2) Symptomatic epilepsies ➜Disorder of CNS 3) Cryptogenic epilepsies ➜Disorder of a hidden course ➜Age related
  • 8. 1)Absence Seizure : ✧(minor epilepsy): prevalent in children, lasts about 1/2 min. Symptoms : ✧Momentary loss of consciousness, ✧patient apparently freeze and stares in one direction, and litte jerking. ✧EEG shows characteristic 3 cycles per secnd spike and wave pattern.
  • 9. 2)Myoclonic seizures ✧ Shock-like momentary contraction of muscles of a limb or the whole body. Tonic-clonic seizures (Major epilepsy commonest, lasts 1–2 min Symptoms : ✧ cry—unconsciousness ✧tonic spasm of all body muscles ✧clonic jerking followed by prolonged sleep and depression of all CNS functions.
  • 10. 3)Atonic seizures (Akinetic epilepsy): Symptoms : Unconsciousness with relaxation of all muscles due to excessive inhibitory discharges. Patient may fall. Tonic phase : ✧Become rigid falls to the ground. ✧Respiration are interrupted. ✧last about 1 mins. Clonic phase : ✧Rapid muscle jerking. ✧Muscle flaccidity. ✧Tongue biting,High salivation.
  • 11. III) Unclassified seizure ✧This seizure may be unclassified due to inadequate information to allow it to be placed in the focal, generalized or unknown onset categories. This includes some neonatal seizures. Neonatal seizure : ✧A seizure is caused by sudden, abnormal and excessive electrical activity in the brain.this seizure produced in baby younger than 4 weeks old.
  • 12. IV) Status epilepticus ✧A seizure that lasts longer than 5 minutes, ✧This types of seizure occurs repeatedly with no recovery of the consciousness.
  • 13. Causes ✧High fever ,Drug use , Alcohol withdrawal. ✧Metabolic disturbances. ✧Head trauma. ✧Brain tumours ,some infections ,Stroke ✧Complication diabetes and pregnancy
  • 16. Cellular mechanisms of seizure generation ✧Excitation (too much) ➜ionic---inward Na⁺ , Ca⁺ ⁺ ➜Neurotransmitter---glutamate,aspartate. ✧Inhibition (too little) ➜Inward---Cl⁻, Outward K⁺ ➜Neurotransmitter---GABA,Glycine
  • 17. Classification of Anti-epileptic drugs 1. Barbiturate Phenobarbitone 2. Deoxybarbiturate Primidone 3. Hydantoin Phenytoin Fosphenytoin 4. Iminostilbene Carbamazepine Oxcarbazepine 5. Succinimide Ethosuximide 6. Aliphatic carboxylic acid Valproic acid. Divalproex (sodium valproate) 7. Phenyltriazine Lamotrigine
  • 18. 8. Benzodiazepines Clonazepam Diazepam Lorazepam Clobazam 9. Cyclic GABA analogues Pregabalin Gabapentin 10. Newer drugs Zonisamide Topiramate Levetiracetam Vigabatrin Tiagabine Lacosamide
  • 20. ☞Pharmacological action ☞Adverse Drug Reaction ☞Use ☞Dose
  • 21. Pharmacological action 1)Barbiturate Phenobarbitone : →Phenobarbitone was the cheapest and less toxic and first efficacious anti-epilepti drug. →Enhancement of GABAA receptor mediated synaptic inhibition appears to be most important mechanism.also act as anti-glutamate activity (Ca⁺ ⁺ reduction) Its produced CNS depression action. ADR : →Long term administration—behavioral abnormalities, learning and memory, hyperactivity in children, mental confusion in older people,Rashes, megaloblastic anaemia and osteo- malacia (similar to that with phenytoin)
  • 22. USE : →This drug is used to Generalized tonic-clonic (GTC), simple partial (SP) and complex partial (CP) seizures.It is not effective in absence seizures. Dose of 60 mg 1–3 times a day in adults; in children (3–5 mg/kg/ day) Status epilepticus: Phenobarbitone sod. may be injected i.m. or i.v. but response is slow to develop
  • 23. 2)Deoxybarbiturate Primidone : →A deoxybarbiturate, converted by liver to phenobarbitone and phenylethyl malonamide (PEMA). primidone is less potent activity.similar mechanism of action of Phenobarbitone. ADR : →similar to phenobarbitone. In addition,anaemia,leukopenia,psychotic reaction and lymph node enlargement occur rarely. USE : →It is infrequently used now in GTCS and partial epilepsy Dose : 250–500 mg, children 10–20 mg/kg/day.
  • 24. 3)Hydantoin Phenytoin (Diphenylhydantoin) ✧It is a major Anti-epileptic drug.It dose not produce CNS depression.some sedation occurs at therapeutic doses. Mechanism of action : ✧It prolonging the inactivated state of voltage sensitive neuronal Na+ channel. ✧As a result high frequency discharges are inhibited with little effect on normal low frequency discharges which allow Na+ channel to recover even when their inactivation is prolonged. ✧while other effects like reduction in Ca2+ influx, inhibition of glutmate and facilitation of GABA responses have been demonstrated.
  • 25. ADR : 1) In therapeutic levels ✧Hirsutism, Hypersensitivity reactions are rashes, lymphadenopathy,neutropenia. ✧Megaloblastic anaemia : decrease folate absorption and it's increase excretion. ✧Osteomalacia : Metabolic activation Vit D / calcium absorption. ✧Hyperglycemia. ✧Used during pregnancy, phenytoin can produce foetal hydantoin syndrome
  • 26. 2)In plasma levels ✧Ataxia,vertigo, drowsiness,behavioral changes,mental confusions, hallucination, rigidity. ✧In taking the during with meals - Epigastric pain, nausea vomiting. ✧i.v - local vascular injury - damaged blood vessels / vein and thrombosis,Cardiac arrhythmias. USE : 1. Generalized tonic-clonic, simple and complex partial seizures. It is ineffective in absence seizures. 2. Status epilepticus: occasionally used by slow i.v. injection (Fosphenytoin replaced it) Dose: 100 mg - 400 mg/day adult ; Children 5–8 mg/kg/day.
  • 27. Fosphenytoin : ✧This is water soluble prodrug. ✧it Difficulties in i.v. administration of phenytoin,which it has replaced for use in status epilepticus. In the body, it is rapidly converted to phenytoin. ✧While phenytoin cannot be injected in a drip of glucose solution (because it gets precipitated),fosphenytoin can be injected with both salin and glucose. ADR : Same as phenytoin Dose : 50 mg/ml in 2 ml, 10 ml inj. (Fosolin)
  • 28. 4)Iminostilbene Carbamazepine : ✧Chemically related to imipramine. ✧Now it is a first line antiepileptic drug ✧Its pharmacological actions resemble phenytoin. ✧It also has antidiuretic action, probably by enhancing ADH action on renal tubules ADR : ✧Neurotoxicity—sedation, dizziness,vertigo, diplopia and ataxia ✧Vomiting, diarrhoea,coma, cardiovascular collapse,rashes, aplastic anaemia,hyponatremia. USE : The most commonly used drug for GTCS and SPS. Dose : Dose: 200–400 mg ; Children 15–30 mg/kg/day.
  • 29. 5)Succinimide: Ethosuximide : ✧Ethosuximide selectively suppresses T current without affectingother types of Ca2+ or Na+ currents. It also doe not potentiate GABA at therapeutic concentions. This correlates well with its selectve action in absence seizure. ADR : ✧Gastrointestinal intolerance, tiredness, mood changes, agitation,headache, drowsiness and inability to concentrate. Hypersensitivity reactions like rashes,No liver or kidney damage. USE : The only indication for ethosuximide is absence seizures.
  • 30. 6)Aliphatic Carboxylic acid: Valproic acid : ✧Valproate produces little sedation or other central effects. Likewise, itis effective in partial seizures and GTCS as well as absence seizures. ✧A phenytoin-like frequency-dependent prolongation of Na+ channel inactivation. ✧Weak attenuation of Ca2+ mediated.(ethosuximide like). ✧Augmentation of release of inhibitory transmitter of GABA
  • 31. ADR : ✧Anorexia, vomiting, loose motions and heart burn are common but mild. Drowsiness, ataxia and tremor are dose-related side effects. ✧Alopecia, curling of hair, weight gain and increased bleeding tendency have been observed Rashes and thrombocytopenia. USE : ✧Valproic acid is the drug of choice for absence seizures ✧Used during pregnancy, it has produced spina bifida. Divalproex (Semisodium valproate) ✧It is the co-ordination compound of valproic acid with sodium valproate. Oral absorption is slow. ✧Same MOA of valproic acid.
  • 32. 7)Benzodiazipines (clonazepam,clobazam,diazepam,lorazepam) ✧Benzodiazepines potentiate GABA induced Cl– influx to produce sedation and the same mechanism has been held responsible for the anticonvulsant property. ADR: ✧Over sedation, dullness,lack of concentration, irritability, ataxia. ✧Salivation and increased respiratory secretion.
  • 33. USE : ➝Clonazepam : primarily used in absence seizure also used as adjuvant in myoclonic sezure ➝Clobazem : Used in partial,GTCS, absence atonic seizure. ➝Diazepam and lorazepam : it is a first line drug for emergency control of convulsions, e.g. status epilepticus, tetanus, eclampsia, convulsant drug poisoning,
  • 34. 8)phenyltriazine Lamotrigine ✧It is new anti-convulsion drug.It act as Prolongation of Na+ channel inactivation. ✧Also preventing release of excitatory neurotransmitters, mainly glutamate and aspartate. ADR : ✧Sleepiness,dizziness,diplopia,ataxia,vomiting. USE : ✧partial seizure,GTCS,absence, myoclonic seizure have been successfuly treated.
  • 35. 9) Cyclic GABA analogue Gabapentin : ✧It is postulated that decreased entry of Ca2+ into the presynaptic neurone through these channels could reduce glutamate release, lowering neuronal excitability. ADR : Mild sedation, tiredness, dizzines. USE : Secondary partial seizure, Complex partial seizure.
  • 36. 10)Newer drugs Topiramate : It appears to act by multiple mechanisms, viz phenytoin like →prolongation of Na+ channel inactivation, →GABA potentiation by a postsynaptic effect, →antagonism of certain glutamate receptors → neuronal hyperpolarization through certain K+ channels →Recently, topiramate has been approved for prophylaxis of migraine; may be used when β blocker. Zonisamide : Selective prolongation of Na+ channel inactivation.
  • 37. levetirecetam : (keppra) ✧MAO is Not exactly know ✧Binds to the synaptic vesicle protein 2A (SV2A) in the brain also regulate the neurotransmitter release. ✧inhibits the release of calcium from intracellular stores. ✧This can likely modify pre synaptic release of glutmate and GABA ADR : Drowsiness, fatigue, dizziness, ataxia. USE : Partial seizure , Tonic clonic seizure myoclonic seizure.
  • 38. Thiagabin : Selective GAT- 1 blocking agent. ADR : Mild sedation, nervousness,asthenia, amnesia, abdominal pain. USE : partial seizure.
  • 39. Vigabatrin : ✧It is an inhibitor of GABA-transaminase, the enzyme which degrades GABA. ✧Anticonvulsant action may be due to increase in synaptic GABA concentration Lacosamide : ✧It acts by enhancing Na+ channel inactivation. ✧Lacosamide is metabolized by CYP2C19 and excreted in urine. USE : partial seizure.
  • 42. Zoho Show To create beautiful presentations, download Zoho Show from Play Store https://zoho.to/cy7 Epilepsy and anti epileptic drugs .pdf (This PDF has been generated using Zoho Show)